Pelubiprofen, represented by the following Chemical Formula 1, (molecular formula: C16H18O3, Mw: 258.31, IUPAC Name: 2-[4-(2-oxocyclohexylidenemethyl)phenyl]propionic acid) is a kind of non-steroidal anti-inflammatory drugs (NSAIDs), derived from cycloalkylidenemethyl phenylacetic acid. NSAIDs show various pharmacological effects including anti-inflammatory, analgesic and antipyretic activities. Pelubiprofen is known to show higher pharmacological effects than the current commercial NSAIDs such as loxoprofen, ketoprofen, ibuprofen, and naproxen.

In this regard, pelubiprofen is disclosed in Japanese Patent No. 1167548 (Japanese Patent Application No. 1977-98121) and the preparation method of pelubiprofen is described in Japanese Patent No. 1637767 (Japanese Patent Application No. 1984-142567).
However, the above Japanese patents give only a mere description of pelubiprofen as a novel compound and the synthesis thereof, respectively, but do not elucidate the specific pharmaceutical formulations of pelubiprofen that is applicable to the body, particularly with regard to oral pharmaceutical formulations.
Korean Patent Publication No. 10-2004-0002890 discloses a percutaneously absorbable patch which is improved in both percutaneous absorption and stability of an anti-inflammatory agent in form of a salt. A sodium salt of pelubiprofen is introduced as an anti-inflammatory agent in the form of a salt.
But, the pharmaceutical formulation disclosed in the Korean Patent is a percutaneously absorbable patch, not an oral pharmaceutical formulation, and the used pelubiprofen is a salt form.
Dosage form design is prerequisite for the application of drugs to the body. “Dosage form design” usually refers to determining optimal pharmaceutical formulation and a dosage regimen which meet optimal conditions for chemical and physical properties, pharmacological actions and therapeutic purposes. In order to exert pharmacological effects thereof, a chemical compound should be formulated into specific forms, such as tablets, capsules, injections, ointments, pastes, etc. Also, the properties of a designed formulation should be supported by concrete experimentation using the dosage forms of the chemical.
Usually, NSAIDs are required to exert the pharmacological effects thereof rapidly. In this context, NSAIDs have been developed as injection formulations, such as subcutaneous and intravenous injections as found in the market. Although advantageous in that their effects are rapid, the injection formulations impart a limitation on their administration.
One of the prerequisites for the development of NSAIDs is a dissolution rate which is high enough to allow them to rapidly exert their pharmacological effects. Typically, improving the dissolution rate of oral pharmaceutical formulations may be achieved by 1) milling particles of active ingredients into small sizes, 2) adding surfactants, 3) atomizing the formulation to nano-sizes, or 4) employing a solid dispersant.
On the whole, the smaller the active ingredient particles are in size, the better the dissolution rates thereof are. Smaller particle sizes of the active ingredients increase the surface areas thereof, however, they result in a greater opportunity to react with the other additives contained in the oral formulation and in turn decrease the stability of the active ingredients.
As such, many different additives other than the active ingredient in an oral pharmaceutical formulation may be more apt to deteriorate the pharmaceutical effects of the active ingredient when its size is smaller. In order to solve this problem, the present inventors have studied the stabilization of oral pharmaceutical formulations with convenience and effectiveness in mind.
Leading to the present invention, intensive and thorough research, conducted by the present inventors, into an oral pharmaceutical formulation of pelubiprofen which has a high dissolution rate with a concomitant maintenance of stability, resulted in the finding that a pelubiprofen particle size ranging from 1 to 30 μm in combination with specific additives greatly improves the dissolution rate and stability of the oral pharmaceutical formulation thereof.